We propose a 5-year continuation of the largest follow-up study of African-American women, the Black Women's Health Study (BWHS). We have followed 59,000 U.S. black women biennially since 1995, collected information on medical, reproductive, lifestyle, psychosocial, and socioeconomic factors, identified incident disease and deaths, and collected cheek cell samples from 26,800 participants. The overarching goal is to elucidate risk factors for cancers with disproportionately high incidence or mortality rates in black women, prominent among which are breast and colorectal cancer, and to elucidate causes of important nonmalignant conditions. Continued follow-up will increase the number of incident breast cancer cases to ~2,400, colorectal cancers to ~500, all-cause deaths to ~3,500, and cancer deaths to ~1,500. Compared with white women, black women have higher breast cancer mortality rates, colorectal cancer incidence and mortality rates, and all- cause and cancer mortality rates. Black women also experience more racism, tend to live in neighborhoods of lower socioeconomic status, have less access to healthy foods, and are more likely to have experienced poverty as children and as adults. Aims of this proposal address aspects of these exposures and outcomes that are of special relevance to black women. Novel aims include the assessment of the relation of experiences of racism to all-cause and cancer mortality; poor diet quality, including restaurant food consumption (fast food), to breast and colorectal cancer incidence and all-cause and cancer mortality; and life-course socioeconomic status to obesity and all-cause and cancer mortality. This proposal also addresses the genetic etiology of breast cancer. Under separate funding, we are assessing two genes, FGFR2 and TNRC9 (which have been associated with breast cancer risk in genome wide association studies of European-ancestry women) to identify SNPs associated with breast cancer risk in the BWHS. Here we propose a novel aim based on those findings, to assess effect modification -- by physical activity, obesity, and reproductive factors -- of associations found in the BWHS in order to identify groups of black women at high risk of breast cancer. Thus, the proposed continuation of the BWHS will provide crucial information for the effort to reduce black/white health disparities. PUBLIC HEALTH RELEVANCE: U.S. black women develop more aggressive breast cancer tumor types and have disproportionately high breast cancer mortality rates, colorectal cancer incidence and mortality rates, and cancer death rates relative to white women. The proposed study will extend data collection in the Black Women's Health Study, the largest follow-up study of U.S. black women, to obtain sufficient cases to assess a range of novel hypotheses concerning behavioral, psychosocial, and socioeconomic factors that may contribute to these differences. Better understanding of the causes of the increased risks among U.S. black women should lead to more effective preventive measures and reductions in health disparities.